Structural Insights for the Stronger Ability of Shrimp Ferritin to Coordinate with Heavy Metal Ions as Compared to Human H-Chain Ferritin

Abstract

Although apoferritin has been widely utilized as a new class of natural protein nanovehicles for encapsulation and delivery of nutraceuticals, its ability to remove metal heavy ions has yet to be explored. In this study, for the first time, we demonstrated that the ferritin from kuruma prawns (Marsupenaeus japonicus), named MjF, has a pronouncedly larger ability to resist denaturation induced by Cd2+ and Hg2+ as compared to its analogue, human H-chain ferritin (HuHF), despite the fact that these two proteins share a high similarity in protein structure. Treatment of HuHF with Cd2+ or Hg2+ at a metal ion/protein shell ratio of 100/1 resulted in marked protein aggregation, while the MjF solution was kept constantly clear upon treatment with Cd2+ and Hg2+ at different protein shell/metal ion ratios (50/1, 100/1, 250/1, 500/1, 1000/1, and 2500/1). Structural comparison analyses in conjunction with the newly solved crystal structure of the complex of MjF plus Cd2+ or Hg2+ revealed that cysteine (Cys) is a major residue responsible for such binding, and that the large difference in the ability to resist denaturation induced by these two heavy metal ions between MjF and HuHF is mainly derived from the different positions of Cys residues in these two proteins; namely, Cys residues in HuHF are located on the outer surface, while Cys residues from MjF are buried within the protein shell. All of these findings raise the high possibility that prawn ferritin, as a food-derived protein, could be developed into a novel bio-template to remove heavy metal ions from contaminated food systems.

Quercetin and Mercury In Vitro Anti-Proliferative Effect in Human Astrocytoma Cells

“…In contrast, both metal compounds deteriorated the tertiary structures of both heme-proteins [35]. In line with this study, Wang and co-workers [36] recently showed that ferritin from Kuruma prawns has a binding capacity to Hg three times larger than that of Cd. The scientific team aimed at exploring the ability of ferritin, a representative member of protein nanocages to remove heavy metal ions from contaminated food systems.…”

“…). It was determined that such coordination mode of Kuruma prawns' ferritin is due to the position of cysteine residues that are buried within the protein shell [36].…”

Multifaceted Applications of Ferritin Nanocages in Delivering Metal Ions, Bioactive Compounds, and Enzymes: A Comprehensive Review

“…98,99 Remarkably, the ferritin of kuruma shrimp (Marsupenaeus japonicus), which shares a high structural similarity with HuHF, has exhibited a superior resistance to denaturation induced by Cd 2+ and Hg 2+ . 100 This differential resilience between MjF and HuHF toward heavy metal ion-induced denaturation could be attributed to the pivotal role of Cys residues in binding with Cd 2+ and Hg 2+ ; while in HuHF these residues are exposed on the outer surface, they are concealed within the protein shell in MjF. Moreover, oyster ferritin manifests resistance against denaturation invoked by Pb 2+ , Cd 2+ , and Cr 3+ , and has been linked to the reduction of high blood lead levels in mice, illustrating its potential in alleviating lead poisoning in vivo.…”

“…Second, ferritin stands as a naturally occurring, innocuous protein with a remarkable affinity for heavy metal ion adsorption, thereby presenting substantial prospects in mitigating heavy metal ion concentrations in food products. It has been substantiated that numerous metal ions can bind and mineralize the inner surface of the ferritin shell, with a series of divalent metal ions serving as inhibitors of ferroxidase activity, inclusive of Mg 2+ , Zn 2+ , Mn 2+ , and Cu 2+ , underscoring the metal adsorption prowess of ferritin. , Remarkably, the ferritin of kuruma shrimp ( Marsupenaeus japonicus ), which shares a high structural similarity with HuHF, has exhibited a superior resistance to denaturation induced by Cd 2+ and Hg 2+ . This differential resilience between MjF and HuHF toward heavy metal ion-induced denaturation could be attributed to the pivotal role of Cys residues in binding with Cd 2+ and Hg 2+ ; while in HuHF these residues are exposed on the outer surface, they are concealed within the protein shell in MjF.…”

New Advances in Iron Metabolism, Ferritin and Hepcidin Research

“…Some papers focused on ferritin. Wang et al [ 1 ] analyzed some properties of ferritin from the shrimp Marsupenaeus japonicus. They found that ferritin resists concentrations of Cd 2+ and Hg 2+ that cause the aggregation of human ferritins.…”